Inhibition of tubulin polymerization in human HCT-116 cells
- Deposit:2024-05-03
- Modify:2024-05-03
Title: Exploration of cytotoxic potential and tubulin polymerization inhibition activity of cis-stilbene-1,2,3-triazole congeners.
Abstract: To scrutinize cis-stilbene based molecules with potential anticancer and tubulin polymerization inhibition activity, a new series of cis-stilbene-1,2,3-triazole congeners was designed and synthesized via a click chemistry protocol. The cytotoxicity of these compounds 9a-j and 10a-j was screened against lung, breast, skin and colorectal cancer cell lines. Based on the results of MTT assay, we further evaluated the selectivity index of the most active compound 9j (IC50 3.25 ± 1.04 μM on HCT-116) by comparing its IC50 value (72.24 ± 1.20 μM) to that of the normal human cell line. Further, to confirm apoptotic cell death, cell morphology and staining studies (AO/EB, DAPI and Annexin V/PI) were carried out. The outcomes of studies showed apoptotic features like change in cell shape, cornering of nuclei, micronuclei formation, fragmented, bright, horseshoe-shaped nuclei, etc. Moreover, active compound 9j displayed G2/M phase cell cycle arrest with significant tubulin polymerization inhibition activity with an IC50 value of 4.51 μM. Additionally, in silico ADMET, molecular docking and molecular dynamic studies of 9j with 3E22 protein proved the binding of the compound at the colchicine binding site of tubulin.
Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Journal: RSC Med Chem
Year: 2023
Volume: 14
Issue: 3
First Page: 482
Last Page: 490
DOI: 10.1039/d2md00400c
Target ChEMBL ID: CHEMBL2095182
ChEMBL Target Name: Tubulin
ChEMBL Target Type: PROTEIN COMPLEX GROUP - Target is a poorly defined protein complex, where subunit composition is unclear (e.g., GABA-A receptor)
Relationship Type: D - Direct protein target assigned
Confidence: Multiple direct protein targets may be assigned
- PubChem
- ChEMBLLICENSEAccess to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).http://www.ebi.ac.uk/Information/termsofuse.html